Nerve cell assemblies in circumscribed regions of the brain are pathologically synchronously active in patients with neurological or psychiatric diseases such as Parkinson's disease, essential tremor, dystonia, functional disturbances after a stroke, migraine, obsessive compulsive disorders, epilepsy, tinnitus, schizophrenia, borderline personality disturbance and irritable bowel syndrome. In this case, a large number of neurons synchronously form action potentials, i.e. the participating neurons fire excessively synchronously. In a healthy person, in contrast, the neurons fire with a different quality, e.g. in an uncorrelated manner, in these brain areas.
In Parkinson's disease, the pathologically synchronous activity in the thalamus and in the basal ganglia changes the neuronal activity in other brain areas, e.g. in areas of the cerebral cortex such as the primary motor cortex. In this respect, the pathologically synchronous activity in the region of the thalamus and of the basal ganglia, for example, imposes its rhythm on the cerebral cortex areas such that ultimately the muscles controlled by these areas develop pathological activity, e.g. a rhythmic trembling (tremor). With chronically subjective tinnitus, pathological synchronous activity is found in a network of auditory and non-auditory brain areas.
In patients with brain diseases and spinal cord diseases that are characterized by excessively synchronized neuronal activity, non-invasively determined spatiotemporal stimulus patterns, in particular “coordinated reset” stimulation (CR stimulation) are applied to achieve permanent relief. The non-invasive CR stimulation can be implemented by means of different stimulation modes;    (i) by sensory stimulation, i.e. by physiological stimulation of receptors such as acoustic stimulation of the inner ear, visual stimulation of the retina or mechanical (e.g. vibrotactile) or thermal stimulation of receptors of the skin, hypoderm, muscles and sinews;    (ii) by stimulation of peripheral nerves (and associated receptors) e.g. by means of electric current (e.g. transcutaneous electrostimulation), by means of magnetic fields (transdermal magnetic stimulation) or by means of ultrasound; and    (iii) by stimulation of the brain or spinal cord e.g. by means of electric current (e.g. external cranial or transcranial neurostimulation), by means of magnetic fields (e.g. transcranial magnetic stimulation) or by means of ultrasound.
Acoustic CR stimulation is used to treat chronically subjective tonal or narrow-band tinnitus. For this purpose, therapeutic sounds are adapted to the dominant tinnitus tone and are applied in the sense of CR stimulation to achieve a long-lasting desynchronization of the pathologically synchronous activity or even a lasting desynchronization thereof that considerably survives the switching off of the stimulation. The acoustic CR stimulation for treating tinnitus effects a significant and considerably pronounced reduction of the symptoms (cf. P. A. Tass, I. Adamchic, H.-J. Freund, T. von Stackelberg, C. Hauptmann: Counteracting tinnitus by acoustic coordinated reset neuromodulation. Restorative Neurology and Neuroscience 30, 137-159 (2012)), a significant reduction of pathological neuronal synchronization in a network of auditory and non-auditory brain areas (cf. P A. Tass, I. Adamchic, H.-J. Freund, T. von Stackelberg, C. Hauptmann: Counteracting tinnitus by acoustic coordinated reset neuromodulation. Restorative Neurology and Neuroscience 30, 137-159 (2012); I. Adamchic, T. Toth, C. Hauptmann, P. A. Tass: Reversing pathologically increased EEG power by acoustic CR neuromodulation. Human Brain Mapping 35 2009-2118 (2014)), a significant reduction of the pathological interactions between different brain areas therein (cf. A. N. Silchenko, I. Adamchic, C. Hauptmann, P. A. Tass: Impact of acoustic coordinated reset neuromodulation on effective connectivity in a neural network of phantom sound. Neuroimage 77, 133-147 (2013)), as well as in different frequency ranges (cf. I. Adamchic, B. Langguth, C. Hauptmann, P. A. Tass: Abnormal brain activity and cross-frequency coupling in the tinnitus network. Frontiers in Neuroscience 8, 284 (2014)).
Parkinson's disease can be treated in an analog manner by means of vibrotactile CR stimulation. Further indications are e.g. represented by epileptic fits, functional disturbances after stroke, chronic pain syndromes (by means of vibrotactile and/or thermal CR stimulation), migraine (e.g. by means of visual CR stimulation). These diseases can furthermore be treated by transcranial magnetic stimulation or by direct electrical stimulation of the brain or direct brain stimulation by means of ultrasound.
All three of the above-named stimulation modalities (i) to (iii) have three substantial disadvantages named in the following:    a) The stimulation effect can vary relevantly from application to application, i.e. from stimulation epoch to stimulation epoch. In other words, the stimulation effect is dependent to a relevant degree on the initial conditions of the organism or nervous system in which the stimulation is started. If e.g. a very good effect is achieved in the one stimulation epoch, this effect will rather be unsatisfactory in a next stimulation epoch.    b) The stimulation success depends too greatly on the stimulus intensity in the previous form of the CR stimulation. Variations of the stimulus intensity can typically not be avoided in non-invasive CR stimulation. E.g. the patients in the acoustic CR stimulation for treating tinnitus adapt the intensity of the CR sounds to the volume of the environmental noise. In vibrotactile CR stimulation, the contact pressure and thus the stimulus intensity can e.g. depend on the base on which the patients support the stimulated extremity together with the vibrotactile actuators. Brightness fluctuations of the environment produce different stimulus strengths in the optical stimulation (e.g. by means of transmission eyeglasses). On the electrical stimulation of the skin, the stimulus strength depends on the conductivity of the skin and thus e.g. on the perspiration and generally on the vegetative state and overall status or heath status of the patient.    c) The stimulus strength must very generally be considered in relation to characteristic parameters of the system to be stimulated, that is of the body or of the nervous system. Since these parameters (e.g. specific ion concentrations, fluid volumes, hormone concentrations, etc.) fluctuate and are e.g. subject to pronounced fluctuations at different times of day, an optimum stimulus strength should either be correspondingly corrected or a stimulation method should be used whose stimulation effects are as independent as possible of these fluctuations.
In summary, the effect of the previously used CR stimulation is not sufficiently robust with respect to fluctuations of the stimulus intensity as well as with respect to characteristic parameters of the organism or nervous system to be stimulated (at the start of the stimulation as well as in the course of stimulation) and the effect of the CR stimulation in particular fluctuates by too much from stimulation epoch to stimulation epoch, i.e. there are too many stimulation epochs with a small effect.